Probiotic in the prevention of ventilator-associated pneumonia in critically ill patients: evidence from meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Probiotic might have a role in the prevention of ventilator-associated pneumonia (VAP) among mechanically ventilated patients, but the efficacy and safety remained inconsistent. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of probiotic (prebiotic, synbiotic) versus placebo in preventing VAP in critically ill patients undergoing mechanical ventilation. METHODS: PubMed, Embase and the Cochrane library databases were searched to 10 October 2021 without language restriction for randomized or semi-randomized controlled trials evaluating probiotic (prebiotic, synbiotic) vs. placebo in prevention of VAP in critically ill mechanically ventilated patients. The pooled relative risk (RR) along with 95% confidence intervals (CI) were combined using a random-effects model. Furthermore, the trial sequential analysis (TSA) and subgroup analyses were performed. Statistical significance was regarded as P < 0.05. RESULTS: Twenty-three trials involving 5543 patients were eligible for this meta-analysis. The combined RR of decreasing the risk of VAP by probiotic was 0.67 (0.56, 0.81) for all eligible studies, 0.69 (n = 5136; 95% CI = 0.57 to 0.84; P < 0.01) for adults studies and 0.55 (n = 407; 95%CI = 0.31 to 0.99; P = 0.046) for neonates/children studies. Additionally, the above-mentioned positive finding in 20 adults studies was verified by the results of TSA, subgroup analyses and cumulative meta-analysis. Ample evidences demonstrated a 31% decrease in RR of incidence of VAP was noted when prophylactic probiotic therapy was administrated among adult patients. Finally, there were no effects on the ICU/hospital/28-/90-day mortality, bacteremia, CRBSI, diarrhea, ICU-acquired infections, infectious complications, pneumonia, UTI and wound infection between two groups (P > 0.05 for all). CONCLUSIONS: Based on the results of our study, the current evidences suggested that prophylactic administration of probiotic might be utilized as a preventive method for VAP in neonates/children and adults patients who required mechanical ventilation. However, further large, high-quality RCTs are warranted to assess the efficacy and safety of probiotic treatment in critically ill patients, especially for the neonates/children studies and the long-term consequences of this therapy.

Association of the rs17250932, rs4794067, and rs2240017 polymorphism in the TBX21 gene with autoimmune diseases: A meta-analysis.

OBJECTIVE: To evaluate systematically the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations. METHODS: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger's regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis. RESULTS: A total of 12 eligible studies, including 3834 patients and 4824 healthy controls, were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms were significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131-1.875, P = 0.004; OR: 0.766, 95% CI: 0.615-0.954, P = 0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239-2.189, P = 0.001; OR: 0.796, 95% CI: 0.634-0.999, P = 0.049), and dominant model (OR: 1.572, 95% CI: 1.194-2.071, P = 0.004; OR: 0.767, 95% CI: 0.607-0.970, P = 0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases, and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was established in this meta-analysis. CONCLUSION: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphism confer susceptibility to autoimmune diseases, but not rs17250932.

[A study on quality of Paridis Rhizoma and consideration on standards of Paridis Rhizoma in Chinese Pharmacopoeia].

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.

[Study on quality characteristics of Ligustri Lucidi Fructus in national resource survey and consideration on standards of Ligustri Lucidi Fructus in Chinese Pharmacopoeia].

The content of tyrosol,salidroside,echinacoside,rutin,acteoside,ligustroflavone,specnuezhenide,and quercetin were determined by HPLC,and the color of Ligustri Lucidi Fructus was determined by comparison with color card.Hundred-seed weight was analyzed by using gravimetric method.The correlation analysis and One-way ANOVA were used to analyze the relationship between the characters,the chemical composition,the harvest time and the geographical location of Ligustri Lucidi Fructus,for giving a comprehensive evaluation of the quality of Ligustri Lucidi Fructus The results showed that 92% of Ligustri Lucidi Fructus were all up to quality standard of Chinese Pharmacopoeia,and the contents of 7 components in Ligustri Lucidi Fructus(except quercetin) were higher than those in samples with black colors.The content of salidroside in Ligustri Lucidi Fructus harvested in June was the highest and the other7 components of Ligustri Lucidi Fructus were relatively high in 8-10 months.According to the quality parameters of Ligustri Lucidi Fructus,the Ligustri Lucidi Fructus from six habitats can not be distinguished effectively.The results showed that there was a certain relationship between the color,harvest season and component content of Ligustri Lucidi Fructus,and the habitats were not related to the quality parameters of Ligustri Lucidi Fructus.The study aimsat providing data support for the resource status of native Ligustri Lucidi Fructus,and a theoretical basis for the revision of standards of Ligustri Lucidi Fructusin the future.

[Comparative study on quality of decoction pieces of Saposhnikovia divaricata with different growth patterns and years and thinking of standard of decoction pieces of S. divaricata in Chinese Pharmacopoeia].

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-ß-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsperennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.

Normal saline versus heparin for patency of central venous catheters in adult patients - a systematic review and meta-analysis.

BACKGROUND: Heparin saline (HS) is theoretically superior to normal saline (NS) for maintaining the patency of central venous catheters (CVCs), but the comparative efficacy of them remains controversial. The aim of this systematic review and meta-analysis was to assess the efficacy of NS versus HS in the maintenance of the patency of CVCs in adult patients. METHODS: We searched PubMed, Embase and the Cochrane library databases. Randomized controlled trials (RCTs) evaluating the use of NS vs. HS to maintain the permeability of CVCs among adult patients were included in our meta-analysis. References of relevant papers were reviewed manually. No language restriction was applied. Non-human studies were excluded. Pooled relative risk (RR) was calculated using a Mantel-Haenszel random-effects model. We also performed subgroup analysis examining the effect of the duration of catheter placement on the outcome. All statistical tests were two-sided using a significance level of 0.05. RESULTS: Ten RCTs involving 7875 subjects (with analysis at patient, catheter, lumen and line access level) were included in this meta-analysis. Whether in terms of pooled or local analysis (RR with 95% confidence interval spans 1), NS can be equally, if not more effective, in keeping the CVCs open. Of studies reporting secondary outcomes (maneuver needed, heparin-induced thrombocytopenia, haemorrhage, central venous thrombosis and catheter-related bloodstream infection), heparinised saline was shown not to be superior to non-heparinised solution. Subgroup analysis in patients with short vs long term CVC placement was consistent with the main outcome partly and in particular for maintenance of catheter patency in patients with a long-term placement i.e. >30 days, the RR was 0.97 (n = 6589; 95% CI = 0.76 to 1.23; P = 0.796). However, for patients in whom the catheter was in place for <30 days, the RR was 1.52 (n = 1286; 95% CI = 1.02 to 2.27; P = 0.041). CONCLUSIONS: Based on the results of this meta-analysis, HS is not superior to NS in reducing CVCs occlusion. But in the short term, the use of HS is slightly superior to NS for flushing catheters from a statistical point of view.

[Changes of chemical constituents in Rubiae Radix et Rhizoma before and after carbonized by UPLC-Q-TOF-MS method].

In order to explore the effect on chemical constituents after carbonized, the changes of chemical constituents in raw and carbonized Rubiae Radix et Rhizoma were analyzed by UPLC-Q-TOF-MS. The research also used principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) for data statistics to find out the main differences on components before and after carbonized. The accurate m/z values of Q-TOF-MS and Q-TOF-MS-MS fragments were applied to identify the structures. The results showed that 6 more discrepant constituents were existed between raw and carbonized Rubiae Radix et Rhizoma. Three constituents were selected as the main discrepant components according to the peak area (276 nm) and identified, as lucidin, xanthopurpurin and 1,3,6-trihydroxy-2-methylanthraquinone. After carbonized, contents of xanthopurpurin and 1,3,6-trihydroxy-2-methylanthraquinone were observably increasing, while lucidin was obviously decreasing. They could be used as the chemical markers for the differentiation between raw and carbonized Rubiae Radix et Rhizoma. The results of this experiment played an important role in the study of processing principle of carbonized Rubiae Radix et Rhizoma. It also provided important evidences for the interpretation of effective material based on carbonized Rubiae Radix et Rhizoma.

[Protective effect of different polar fractions of Carbonized Rubiae Radix et Rhizoma (cRRR) against oxidative injury].

The protective effect of different polar fractions of Carbonized Rubiae Radix et Rhizoma (cRRR) against ox-LDL-induced damage to human umbilical vein endothelial cells (HUVECs) was investigated by MTT assay, and the components were identified by using UPLC-Q-TOF-MS. According to the study, ethyl acetate extract and n-butanol extract could increase cell viability (P<0.01), while petroleum ether extract had no influence, and water extract could even inhibit the cell viability to some degree. Moreover, 32 compounds in four polar fractions were analyzed, including 31 quinones and their glycosides, and one rubiprasins C. Petroleum ether extract, ethyl acetate extract, n-butanol extract and water extract contained 23, 32, 26, 15 compounds, respectively. According to cell experiments in vitro, active fractions were ethyl acetate extract and n-butanol extract. The results could provide scientific references for further studies on effective material basic of cRRR, and lay a foundation for studies on the relationship between efficacies and materials.

Crystal structure of hydro-cortisone 17-butyrate.

In the title compound, C25H36O6, the two central cyclo-hexane rings exhibit a chair conformation. The terminal cyclo-hexene and cyclo-pentane rings are in half-chair and envelope conformations (with the C atom bearing the methyl substit-uent as the flap), respectively. The methyl group of the butyrate chain is disordered over two orientations, with a refined occupancy ratio of 0.742 (6):0.258 (6). Intra-molecular O-H⋯O and C-H⋯O hydrogen bonds are observed. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds into chains running parallel to the a axis.

[Derivative synchronous fluorimetry for determination of synthetic food dyes in food].

The first order derivative synchronous fluoremetry was proposed for simultaneous determination of sunset yellow and ponceau 4R The effect of different experimental conditions, such as different pH for character of fluorescence spectra and the choosing of the optimal wavelength difference were studied. It was showed that the zero-crossing points were at 313. 6 nm for ponceau 4R and at 302. 8 nm for sunset yellow in first order derivative synchronous fluorescence spectra. Therefore, 313. 6 and 302. 8 nm were selected for the determination of sunset yellow and ponceau 4R when delta lambda= 130 nm. This method could minimize interference without preseparation. The linear ranges of sunset yellow and ponceau 4R were from 0. 1 to 2. 0 mg L-1 and from 0. 1 to 4. 0 mg L-1 with correlation coefficient 0. 996 6 and 0. 999 2, the detection limits were 0. 041 and 0. 019 mg L-1 , RS-Ds were 4. 6% and 4. 8% (n=6), respectively. The recoveries varied from 91. 0% to 110%. The proposed method was successfully applied in simultaneous determination of sunset yellow and Ponceau 4R in food.

The effect of tourniquet use in total knee arthroplasty: grading the evidence through an updated meta-analysis of randomized, controlled trials.

PURPOSE: Although tourniquets are widely used in total knee arthroplasty (TKA), the effectiveness and safety are still in controversy. We therefore conducted an updated meta-analysis to compare the outcomes of tourniquet-assisted to non-tourniquet-assisted TKA and provide recommendations for using tourniquet in TKA. METHODS: A systematic search of studies published through March 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. Randomized, controlled trials that assessed the influence of the use of a tourniquet in TKA and provided data on safety and clinical effects were identified. Demographic characteristics, adverse events, and clinical outcomes were manually extracted from all of the selected studies. The evidence quality levels and recommendations were assessed using the GRADE system. RESULTS: Fifteen studies encompassing 804 patients and comparing TKA with and without the use of a tourniquet met the inclusion criteria. Overall, the result of meta-analysis indicated that using a tourniquet could decrease the intraoperative blood loss but could increase the postoperative blood loss. However, there was no statistically significant difference in calculated blood loss and measured total blood loss between the tourniquet and non-tourniquet group. There was no statistically significant difference in operation time. Patients treated with a tourniquet might not have higher risks of thromboembolic complications, such as deep vein thrombosis and pulmonary thromboembolism. The overall GRADE system evidence quality was very low, which lowers our confidence in their recommendations. CONCLUSION: As a safe application, the use of a tourniquet during TKA may be effective for reducing intraoperative blood loss, but not for reducing the postoperative blood loss and actual total blood loss. However, no uniform guideline can be made based on the current evidence because of the very low evidence quality and lower GRADE recommendation strength.

COVID-19-induced acute loss of consciousness in Marchiafava-Bignami disease: a case report.

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.

Relationship between initial red cell distribution width and ΔRDW and mortality in cardiac arrest patients.

AIMS: There has been a lack of research examining the relationship between red cell distribution width (RDW) and the prognosis of cardiac arrest (CA) patients. The prognostic value of the changes in RDW during intensive care unit (ICU) hospitalization for CA patients has not been investigated. This study aims to investigate the correlation between RDW measures at ICU admission and RDW changes during ICU hospitalization and the prognosis of CA patients and then develop a nomogram that predicts the risk of mortality of these patients. METHODS AND RESULTS: A retrospective cohort study is used to collect clinical characteristics of CA patients (>18 years) that are on their first admission to ICU with RDW data measured from the Medical Information Mart for Intensive Care IV Version 2.0 database. Patients are randomly divided into a development cohort (75%) and a validation cohort (25%). The primary outcome is 30 and 360 day all-cause mortality. ΔRDW is defined as the RDW on ICU discharge minus RDW on ICU admission. A multivariate Cox regression model is applied to test whether the RDW represents an independent risk factor that affects the all-cause mortality of these patients. Meanwhile, the dose-response relationship between the RDW and the mortality is described by restricted cubic spine (RCS). A prediction model is constructed using a nomogram, which is then assessed using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). A total of 1278 adult CA patients are included in this study. We found that non-survivors have a higher level of RDW and ΔRDW compared with survivors, and the mortality rate is higher in the high RDW group than in the normal RDW group. The Kaplan-Meier survival curve indicates that patients in the normal RDW group had a higher cumulative survival rate at 30 and 360 days than those in the high RDW group (log-rank test, χ2  = 36.710, χ2  = 54.960, both P values <0.05). The multivariate Cox regression analysis shows that elevated RDW at ICU admission (>15.50%) is an independent predictor of 30 [hazard ratio = 1.451, 95% confidence interval (CI) = 1.181-1.782, P < 0.001] and 360 day (hazard ratio = 1.393, 95% CI = 1.160-1.671, P < 0.001) all-cause mortality among CA patients, and an increase in RDW during ICU hospitalization (ΔRDW ≥ 0.4%) can serve as an independent predictor of mortality among these patients. A non-linear relationship between the RDW measured at ICU admission and the increased risk of mortality rate of these patients is shown by the RCS. This study established and validated a nomogram based on six variables, anion gap, first-day Sequential Organ Failure Assessment score, cerebrovascular disease, malignant tumour, norepinephrine use, and RDW, to predict mortality risk in CA patients. The consistency indices of 30 and 360 day mortality of CA patients in the validation cohort are 0.721 and 0.725, respectively. The nomogram proved to be well calibrated in the validation cohort. DCA curves indicated that the nomogram provided a higher net benefit over a wide, reasonable range of threshold probabilities for predicting mortality in CA patients and could be adapted for clinical decision-making. CONCLUSIONS: Elevated RDW levels on ICU admission and rising RDW during ICU hospitalization are powerful predictors of all-cause mortality for CA patients at 30 and 360 days, and they can be used as potential clinical biomarkers to predict the bad prognosis of these patients. The newly developed nomogram, which includes RDW, demonstrates high efficacy in predicting the mortality of CA patients.

Potential mediation effect of insulin resistance on the association between iron metabolism indicators and non-alcoholic fatty liver disease.

OBJECTIVES: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. METHODS: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. RESULTS: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. CONCLUSION: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.

[Association of RNASET2 gene polymorphisms and haplotypes with Graves disease in Han Chinese population from coastal regions of Shandong].

OBJECTIVE: To assess the association of RNASET2 gene polymorphisms and haplotypes with Graves disease (GD) in Han Chinese population from coastal regions of Shandong Province. METHODS: A total of 471 GD patients and 472 controls were enrolled. Genotypes of single nucleotide polymorphisms (SNPs) in RNASET2 gene were determined with a Taqman probe on a Fluidigm EPl platform. Haplotypes and their frequencies were analyzed with a SHEsis online software. RESULTS: There was a significant difference in allele frequencies of rs3777722, rs3777723 and rs9355610 between the GD patients and the controls (P=0.018; P=0.028; P=0.021).Allele frequencies of rs3777722 and rs9355610 were significantly lower in GD than in the controls (P=0.018, P=0.021). Haplotypes A-A-C-A and A-A-T-A were significantly more common in the control group compared with the GD group (P=0.046, OR=0.448, 95%CI:0.200-1.006; P=0.049, OR=0.823, 95%CI:0.678-0.999). The frequency of C-G-C-G haplotype was significantly higher in GD patient group than the control group (P=0.018). CONCLUSION: RNASET2 gene polymorphisms and haplotypes are associated with GD in Han population from coastal areas of Shandong Province. rs3777722 and rs9355610 may contribute to the risk for GD.

Association between inflammatory bowel disease and Parkinson's disease: a prospective cohort study of 468,556 UK biobank participants.

Introduction: Inflammatory Bowel Disease (IBD) and Parkinson's disease (PD) are both chronic, progressive disorders. As such, given the inconclusive results of extensive research on the association between IBD and PD, our study intends to examine this relationship further using the UK Biobank database. Methods: We conducted a prospective cohort study using the Cox proportional hazards model, analyzing data from the UK Biobank to investigate the relationship between IBD and PD, following subjects until PD diagnosis, loss to follow up, death or study termination on 30 June, 2023. Results: The results show that IBD had no effect on the risk of PD (HR: 1.356, 95% CI: 0.941-1.955, p = 0.103), and the effect remained consistent in specific Crohn's disease, ulcerative colitis or unclassified IBD populations. In addition, after sensitivity analysis using propensity matching scores and excluding patients diagnosed with PD 5 or 10 years after baseline, IBD had no effect on the risk of PD. However, in the subgroup analysis, we found that in females (HR: 1.989, 95% CI: 1.032-3.835, p = 0.040), the polygenic risk score was highest (HR: 2.476, 95% CI: 1.401-4.374, p = 0.002), and having ulcerative colitis without hypertension (HR: 2.042, 95% CI: 1.128-3.697, p = 0.018) was associated with an increased risk of PD. Conclusion: In conclusion, over an average follow-up period of 13.93 years, we found no significant association between IBD and PD.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells.

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

[The relationship between C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma].

OBJECTIVE: To explore the association of C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma (ESCC). METHODS: Purification of genomic DNA from whole blood was used the Maxwell(16) System. rs3746804 in C20orf54 was detected by direct sequencing in 434 ESCC patients from Changzhi (Shanxi province) and Linzhou (Henan province) and 554 healthy controls from Changzhi, Linzhou and including immigrators from Linzhou to Changzhi. RESULTS: For rs3746804, the genotypic frequencies of CT (37.5% vs 51.0%, 37.5% vs 52.0%), CC (44.2% vs 34.8%, 44.2% vs 33.0%) in Changzhi ESCC patients showed significant differences with healthy Changzhi controls and the healthy immigrator controls (all P < 0.05), and the frequencies of TT (18.3% vs 4.1%) and CC (44.2% vs 54.6%) in Changzhi ESCC patients showed significant differences with Linzhou ESCC patients (all P < 0.05). The genotypic frequencies of TT (4.1% vs 15.0%), CT (41.2% vs 52.0%) and CC(54.6% vs 33.0%) showed significant differences between Linzhou ESCC patients and the healthy immigrator controls (all P < 0.05), and the frequencies of TT (4.1% vs 14.1%) and CC(54.6% vs 34.8%) showed significant differences between Linzhou ESCC patients and Changzhi healthy controls (all P < 0.01). Meanwhile, there were significant differences between ESCC patients (including Changzhi and Linzhou ESCC patients) and healthy controls (including the healthy Changzhi, Linzhou and immigrator controls) in genotypic frequencies of CT (39.2% vs 48.7%) and CC (48.8% vs 38.2%) (all P < 0.01). CT and CT + TT genotype could decrease the risk of ESCC compared with the CC genotype (OR = 0.630, 95%CI 0.481 - 0.826; OR = 0.654, 95%CI 0.507 - 0.844). CONCLUSION: There is a closed relationship between SNP rs3746804 in C20orf54 and susceptibility to ESCC.

[Correlation of H-type hypertension and prognosis of ischemic stroke].

OBJECTIVE: To examine the correlation between hypertension with hyperhomocysteinemia and prognosis of ischemic stroke. METHODS: A total of 634 patients with acute ischemic stroke confirmed by computed tomography or magnetic resonance imaging were recruited at Department of Neurology, First Affiliated Hospital, Zhengzhou University from January 1, 2007 to May 30, 2010. Their NIHSS (National Institute of Health Stroke Scale) scores were evaluated on admission. And their baseline profiles and probable prognostic factors were recorded. Recovery was assessed by modified Rankin score (MRS) during a 6-month follow-up. Multivariate Logistic regression was performed for statistical analysis. RESULTS: Among them, 32 became lost to follow-up. There were 197 females (32.7%) and 405 males (67.3%) with an average age of (59 ± 13) years (range: 19 - 92). The average level of homocysteine was (19 ± 11) µmol/L. There were 343 (57%) patients with hypertension and MRS ≥ 3 was in 145 (31%) patients. Logistic regression analysis showed that significant correlations existed between H-type hypertension and 6-month MRS (P = 0.012, OR = 2.566, 95%CI: 1.299 - 5.357) when homocysteine ≥ 15 µmol/L was defined for hyperhomocysteinemia. And there was a total sum of interaction between hypertension and hyperhomocysteinemia. The parameters of relative excess risk of interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S) were 0.683, 26.61% and 1.59 respectively. Other parameters with significant prognostic correlations included age, history of stroke, NIHSS score on admission and diastolic blood pressure on admission. CONCLUSION: At the homocysteine level of ≥ 15 µmol/L, H-type hypertension and 6-month MRS have significant correlations. And H-type hypertension is a risk factor for the prognosis of ischemic stroke. When hypertension and hyperhomocysteinemia coexist, there is a total sum of interaction.

[Risk factors for acquired multidrug-resistant Acinetobacter baumannii colonization in respiratory intensive care unit].

OBJECTIVE: To determine the risk factors for respiratory intensive care unit (RICU)-acquired colonization of multidrug-resistant Acinetobacter baumannii (MDR-AB). METHODS: From January 2010 to June 2011, active screening was performed to define patients with RICU-acquired colonization of MDR-AB. And environment surveillance was carried out and patient data were collected. Logistic regression was applied to identify the risk factors of RICU-acquired colonization of MDR-AB. RESULTS: Active screening for MDR-AB was performed for 110 patients in RICU and 50 patients turned out to be positive. After eliminating 3 input positive patients, the RICU-acquired colonization rate of MDR-AB was 43.9% (47/107). The environmental contaminated rate of MDR-AB was 66.0% (31/47) for 47 positive patients and 33.9% (19/56) for 56 negative ones (χ(2) = 10.494, P < 0.01). Five risk factors were associated with the colonization of MDR-AB through univariate analysis: consciousness disturbance, use of carbapenems, nasal feeding tube, endotracheal intubation and mechanical ventilation (all P < 0.05). The Logistic regression equation contained 3 risk factors of conscious disturbance, use of carbapenems and mechanical ventilation (OR = 3.412, 3.211, 3.002; 95% CI: 1.165 - 9.992, 1.117 - 9.233, 1.101 - 8.182). CONCLUSION: Three risk factors are independently associated with the RICU-acquired colonization of MDR-AB: consciousness disturbance, use of carbapenems and mechanical ventilation.